Interleukin-2 increased the proportion of regulatory T cells (Tregs) in patients with hepatitis C virus (HCV)-induced vasculitis and in those with chronic graft-versus-host disease.Low-dose interleukin-2 immunotherapy appears to be safe and effective in treating two immune-mediated diseases, two small, uncontrolled studies showed.

In the first study, David Klatzmann, MD, PhD, of Pierre and Marie Curie University in Paris, and colleagues found that interleukin-2 increased the proportion of regulatory T cells (Tregs) in all 10 patients with hepatitis C virus (HCV)-induced vasculitis and improved symptoms of vasculitis in eight, with few side effects.

In the second study, John Koreth, MBBS, DPhil, of the Dana-Farber Cancer Institute in Boston, and colleagues found that the treatment induced partial responses in about half of patients with chronic graft-versus-host disease (GVHD), with no cases of relapse or progression of the disease.

The results of both studies -- which were reported in the Dec. 1 issue of the New England Journal of Medicine -- "signal a major shift in the therapeutic use of interleukin-2," according to Jeffrey Bluestone, PhD, of the University of California San Francisco.

Overall, the treatment appeared to be safe, but the long-term effects are uncertain, he wrote in an accompanying editorial.

"Thus, these articles and others have provided a path forward for the effective use of interleukin-2 as a regulatory immunotherapy," he concluded. "Future trials involving larger numbers of patients and appropriate control groups are needed to determine the efficacy of not only interleukin-2 therapy but also other approaches to improving Treg numbers and function in autoimmune diseases and GVHD and inhibiting them in cancer."

Klatzmann and colleagues examined whether interleukin-2 could be used to treat patients with vasculitis induced by HCV that does not respond to standard antiviral therapy, rituximab (Rituxan), or both. Interleukin-2 is approved for use as an adjunctive treatment for renal cell carcinoma. It promotes survival and function of Treg cells, which inhibit immune responses.

The study included 10 patients with mixed cryoglobulinemic vasculitis who were not receiving glucocorticoid or immunosuppressant therapy (median age 58.5).

The patients received one course of interleukin-2 at 1.5 million IU per day for five days, followed by three five-day courses of 3 million IU/day at weeks three, six, and nine.

By week nine, there was a significant increase in the proportion of CD4+ T cells that were Tregs -- from 3.6% to 11.8% (P=0.004). That improvement met the primary endpoint of at least a 4% absolute increase.

Nine of the 10 patients also had a reduction in cryoglobulinemia, eight patients saw an improvement in vasculitis, and there was an overall reduction in the expression of genes related to inflammation and oxidative stress.

The treatment appeared to be safe, with no adverse events higher than grade 1 and no significant changes in circulating levels of granulocytes, red cells, or liver enzymes.

In addition, the treatment did not increase the numbers of effector T cells or induce vasculitis flare or increased HCV viremia.

"Further studies are needed to determine whether this intervention could be further modified and whether it would also be effective in the treatment of other inflammatory and autoimmune diseases, such as atherosclerosis or type 1 diabetes," Klatzmann and colleagues concluded.

Koreth and colleagues evaluated interleukin-2 as a treatment option for patients with chronic GVHD, which develops in more than half of patients who have undergone allogeneic hematopoietic stem cell transplantation.

The study included 29 patients (median age 49.5) whose disease did not respond to systemic glucocorticoid therapy.

For eight weeks, patients received daily, low-dose subcutaneous interleukin-2 -- escalating from 300,000 IU per square meter of body-surface area to 1 million IU, then to 3 million IU, if tolerated. The highest dose, however, ... resulted in unacceptable constitutional symptoms, including fever, malaise, and arthralgia, so the maximum tolerated dose was 1 million IU.

None of the patients had a relapse or progression of chronic GVHD, clinical flares, or relapses of an underlying hematologic cancer.

Numbers of CD4+ Treg cells increased in all patients, although of the 23 who could be evaluated for a clinical response, 12 had a partial response involving multiple sites and 11 had stable disease.

The peak median number of CD4+ Treg cells at four weeks was more than eight times higher than at baseline (P<0.001), without any change in the conventional T cells.

For patients who continued to receive interleukin-2 beyond the initial treatment period, the immunologic and clinical response was sustained and the glucocorticoid dose could be tapered by an average of 60%.

The researchers said that the treatment had an acceptable side-effect profile. It did not induce significant leukopenia, neutropenia, thrombocytopenia, or hepatic dysfunction.

Two patients developed grade 4 thrombotic microangiopathy-associated renal failure requiring dialysis, but they were also taking sirolimus (Rapamune) plus tacrolimus.

"Plenty of people are still dying of diseases which other people do not believe." (Dr. M.N.C. Dukes).CBT and GET for ME: "There is no nonsense so gross that society will not, at some time, make a doctrine of it and defend it with every weapon of communal stupidity."

Robertson Davies

THE NICEGUIDELINES BLOG VERSUS THE NICEGUIDELINES

These are NOT the NICEGuidelines. This is "The NICEGUIDELINES BLOG." What are the differences:

The NICE Guidelines are biased publications based on the GOBSART (Good Old Boys Sitting Around a Table) approach.

This Blog however is not only evidence based but also uses critical reading to judge papers and articles. I also use common sense and listen to others. And finally I read both psychiatric and medical evidence and opinions from around the world to come to a conclusion.

I’m not sponsored by anybody or paid by whatever company as seems to be the norm with many psycho people who publish the same article almost on a weekly base.

So if you value an opinion, formed as a result of participating in many ME activities, for example being bed bound for years, you have come to the right BLOG. All these activities have allowed me to form an opinion as a Doctor and as a Patient. And that is important as the voice of the latter is discarded by many including NICE.

If you don’t read this blog, you will miss out on “accredited” medical education. If you do read it, you may actually become a doctor who doesn’t stop thinking or forgets to ask critical questions. Many good things, including satisfied patients are at your command.

So, if you arrived here for the straightforward GOBSART approach, I will disappoint you. If you are interested in forming your own opinion about ME, and other interesting things, read on!

About Dr. Speedy.

I am a Family Physician or GP as it is called in Australia or the UK. I am also an ME patient unfortunately. Bedbound that is. So at the moment I’m in private practice so to speak. I’ve got only one patient, ME, or is it me?

I graduated as a doctor a long time ago, and I am the founder and editor of The NICEGUIDELINES BLOG, an internet based ME BLOG that is devoted to critical reading and cheering you or ME up.

I have the following conflict of interest: I would like to get better and see that the wasting of public money on CBT (talk therapy for a neurological disease, really helpful) and other silly therapies for ME stops, and will be used in better ways.

My goal has always been to help, and if possible, cure patients. With this disease you will soon find out that many psychiatrists and psychologists are only in it to make money and get their name in the spotlight. And what happens to and with the patients is irrelevant.

I stand to benefit both mentally, physically and also financially if this silliness would stop, and I would get my health back, and I can go back to work and have a normal life again. Please evaluate my postings with this in mind! And remember, there are also (lots of) psychiatrists and psychologists who haven’t switched their brain off.